BI 2536

Catalog No.S1109 Batch:S110907

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Technical Data

Formula

C28H39N7O3

Molecular Weight 521.66 CAS No. 755038-02-9
Solubility (25°C)* In vitro DMSO 100 mg/mL (191.69 mM)
Ethanol 100 mg/mL (191.69 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 95% Corn oil
1.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
4.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 80 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description BI-2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM in a cell-free assay. BI-2536 inhibits Bromodomain 4 (BRD4) with Kd of 37 nM and potently suppresses c-Myc expression. BI-2536 induces apoptosis and attenuates autophagy. Phase 2.
Targets
c-Myc [3] PLK1 [1]
(Cell-free assay)
PLK2 [1]
(Cell-free assay)
PLK3 [1]
(Cell-free assay)
BRD4 [3]
(Cell-free assay)
0.83 nM 3.5 nM 9.0 nM 37 nM(Kd)
In vitro

BI 2536 blocks the activities of Plk2 and Plk3 to a slightly lesser extent with IC50 of 3.5 nM and 9.0 nM, respectively. In HeLa cells, BI 2536 treatment ranging from 10-100 nM leads to the blocking of the recruitment of γ-tubulin and phosphorylation of Apc6 at mitotic centrosomes, inhibition of cohesin release from chromosome arms, induction of monopolar spindles, as well as a range of other mitotic processes that are known to depend on Plk1. BI 2536 treatment leads to the HeLa cells arrested in G2/M, subsequently a sub-G1 DNA peak indicative of DNA breakdown and apoptosis, and accumulated cleaved PARP p85 fragments in a concentration-dependent manner. BI 2536 inhibits the growth of a panel of 32 human cancer cell lines with EC50 of 2-25 nM, while blocking the proliferation of exponentially growing hTERT-RPE1, human umbilical vein endothelial cells (HUVECs), and normal rat kidney (NRK) cells with EC50 of 12-31 nM. [1] Plk1 inhibition by BI 2536 reduces the growth and viability of anaplastic thyroid carcinoma (ATC) cells such as CAL62, OCUT-1, SW1736, 8505C, and ACT-1 with EC50 values of 1.4-5.6 nM. [2]

In vivo

BI 2536 given i.v. once or twice per week is highly efficacious in diverse xenograft models with acceptable tolerability by inhibiting cell proliferation through a mitotic arrest, and subsequently induction of tumor-cell death. Administration of BI 2536 at 50 mg/kg once or twice per week significantly inhibits growth of HCT 116 xenografts with T/C of 15% and 0.3%, respectively. BI 2536 treatment twice-weekly also leads to excellent tumor-growth in BxPC-3 and A549 models with T/C of 5% and 14%, respectively. [1]

Features The first potent and selective Plk1 inhibitor that induces all hallmarks of Plk1 inhibition.

Protocol (from reference)

Kinase Assay:

[1]

  • Plk1 in vitro kinase assay

    Recombinant human Plk1 (residues 1-603) is expressed as N-terminal, GST-tagged fusion protein with a baculoviral expression system and purified by affinity chromatography with Glutathione-agarose. Enzyme activity assays for Plk1 are performed in the presence of serially diluted BI 2536 with 20 ng of recombinant kinase and 10 μg casein from bovine milk as the substrate. Kinase reactions are performed in a final volume of 60 μL for 45 minutes at 30 °C (15 mM MgCl2, 25 mM MOPS [pH 7.0], 1 mM DTT, 1% DMSO, 7.5 mM ATP, 0.3 μCi γ-33P-ATP). Reactions are terminated by the addition of 125 μL of ice-cold 5% TCA. After transfer of the precipitates to Multi-Screen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curve is used for calculating IC50 value.

Cell Assay:

[1]

  • Cell lines

    HeLa, A43, SKOV-3, HT-29, K562, A549, Saos-2, MCF7, HCT116, COLO 205, Hep G2, Raji and PC-3 cells, etc.

  • Concentrations

    Dissolved in DMSO, final concentrations ~1 μM

  • Incubation Time

    24 and 72 hours

  • Method

    Cells are exposed to various concentrations of BI 2536 for 24, and 72 hours. Cell growth is assessed by the measurement of Alamar Blue dye conversion in a fluorescence spectrophotometer. For determining the DNA content of the cultures, cell suspensions are fixed in 80% ethanol, treated for 5 minutes with 0.25% Triton X-100 in PBS, and incubated with 0.1% RNase and 10 μg/mL propidium iodide (PI) in PBS for 20 minutes at RT. Cell-cycle profiles are determined by flow cytometric analysis.

Animal Study:

[1]

  • Animal Models

    Female BomTac:NMRI-Foxn1nu mice injected subcutaneously with HCT 116, NCI-H460, or A549 cells

  • Dosages

    ~50 mg/kg

  • Administration

    Injection i.v. once or twice per week

Customer Product Validation

Data from [J Biomol Screen, 2013, 18(1), 54-66]

Data from [J Biomol Screen, 2013, 18(1), 54-66]

Data from [J Biol Chem, 2012, 287(21), 17088-99]

Data from [Nat Cell Biol, 2011, 13, 1265-71]

Selleck's BI 2536 has been cited by 303 publications

The Eμ-Ret mouse is a novel model of hyperdiploid B-cell acute lymphoblastic leukemia [ Leukemia, 2024, 38(5):969-980] PubMed: 38519798
Therapeutic targeting of PLK1 in TERT promoter-mutant hepatocellular carcinoma [ Clin Transl Med, 2024, 14(5):e1703] PubMed: 38769666
Therapeutic targeting of PLK1 in TERT promoter-mutant hepatocellular carcinoma [ Clin Transl Med, 2024, 14(5):e1703] PubMed: 38769666
Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation [ Cell Rep, 2024, 43(9):114739] PubMed: 39276350
Proteomic analysis reveals a PLK1-dependent G2/M degradation program and a role for AKAP2 in coordinating the mitotic cytoskeleton [ Cell Rep, 2024, 43(8):114510] PubMed: 39018246
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis [ Nature, 2023, 621(7978):415-422] PubMed: 37674080
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis [ Nature, 2023, 621(7978):415-422] PubMed: 37674080
Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug-Gene Networks: From Biology to Precision Therapeutics [ Circulation, 2023, 148(19):1459-1478] PubMed: 37850387
Molecular landscape and functional characterization of centrosome amplification in ovarian cancer [ Nat Commun, 2023, 14(1):6505] PubMed: 37845213
Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1 [ Nat Commun, 2023, 14(1):6088] PubMed: 37773176

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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